1. Field of the Invention
The present invention relates to a temperature controller for controlling the temperature of a part of a structure such as a biochemical reaction cassette.
2. Description of the Related Art
For rapid and precise detection of a target nucleic acid in a nucleic acid sample and analysis of the nucleic acid base sequence, various methods are known which utilize a hybridization reaction with a probe carrier. The typical probe carrier for the hybridization reaction is a SNA microarray which immobilizes, on a bead or a glass plate, a probe having a base sequence complementary to the target nucleic acid.
This DNA microarray is promising for medical diagnosis for identifying a pathogen, and for genetic diagnosis for inspecting the physical feature of a patient. For practicing such diagnosis inspection, simplification of the operation is necessary for higher efficiency of the data analysis and examination. However, the inspection conducted with a probe bared on the surface of the immobilizing member can cause undesirable contact of a foreign object with the base plate of a microarray. This can cause defect or contamination of the probe, making difficult the precise inspection. Therefore, the operator should carefully handle the DNA microarray not to touch the base plate with a finger or the like. This may lower the efficiency of inspection. For higher efficiency of the analysis and inspection, several structures of biochemical reaction cassettes were disclosed, in which the microarray is placed in a reaction chamber to conduct the hybridization reaction in the reaction chamber and the detection is conducted thereafter.
During the hybridization reaction in such a biochemical reaction cassette, the temperature of the DNA microarray and the reaction chamber should be controlled at a prescribed temperature. The temperature can be controlled effectively by bringing a face of a heat-conducting member into contact with a face of the base plate of the DNA microarray.
FIG. 7 illustrates a known incubator device disclosed in Japanese Patent Application Laid-Open No. 2005-269906. The incubator device shown in FIG. 7 has reaction vessel 70, temperature controller 72, heat-conducting plate 100, and high-temperature-conducting sheet 102. For constituting the incubator device, firstly a heat-conductive plate having a temperature controller in contact with the lower face is placed horizontally, and thereon, high-temperature-conducting sheet 102 and reaction vessel 70 are placed in the named order. Heat insulation plate 80 is placed detachably on reaction vessel 80 to reduce the influence of outside temperature and to prevent contamination. The heat insulation plate is fixed by resin plate 84.
Box-shaped cover 90 is provided to cover heat insulation plate 80 and resin plate 84. Springs 92 are provided between cover 90 and resin plate 84. When the cover is closed, springs 92 apply pressure against the resin plate and through the heat insulation plate against reaction vessel 70 and to pressure-contact reaction vessel 10 with high-temperature conduction sheet 102.
With the above constitution, box-shaped cover 90 placed on the incubator device applies a pressure through springs 92 to the reaction vessel to strengthen the contact between the reaction vessel and the high-temperature conducting sheet to lower the contact thermal resistance and to increase the efficiency of heat conduction from temperature controller 72 to reaction vessel 70.
The incubator device disclosed in the above-mentioned Japanese Patent Application Laid-Open No. 2005-269906 is advantageous in heat conduction to the entire reaction vessel. However, in the case where the amount of the reactant is small and occupies only a part of the reaction vessel, the entire reaction vessel need not be temperature-controlled. In this case, uniform heating of the entire reaction vessel including a portion requiring no temperature control is inefficient in view of the heating efficiency.
Further, in use of the biochemical cassette, the flow rate of the solution in the reaction chamber should be precisely controlled during the biochemical reaction. For the flow rate control, the posture of the biochemical reaction cassette is preferably fixed to some extent during the biochemical reaction. When the above prior art technique is employed without modification, the biochemical reaction cassette is held directly by the elastic member, which makes it difficult to control precisely the posture of the biochemical reaction cassette.
In the case where a heat-conductive solid member is brought into direct contact with the biochemical cassette, care should be taken not to cause point contact of the heat-conductive solid member with a part of the structure to prevent nonuniform heat conduction.
From the above-mentioned consideration, for local heat control of the structure, the two measures below should be taken simultaneously:
(1) A pressure is applied to the biochemical cassette to bring the heat-conductive member for temperature control into face-to-face contact with a part of the structure; and
(2) The biochemical reaction cassette is held with dynamic balance entirely to keep its posture.
To solve the above problems, the present invention intends to provide a temperature controller suitable for controlling a part of a biochemical reaction cassette.
The temperature controller is applicable not only for temperature control of the aforementioned biochemical reaction cassette but also widely for heating locally a general structure.